| 87% |
With potassium acetate; acetic acid at 90℃; |
1' 2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline- 1 ,3-dione (D- 1)
General procedure: In a 20 mL glass vial, a mixture of 3-hydroxyphthalic anhydride (500 mg, 3.05 mmol, 1 equiv), potassium acetate (927 mg, 9.44 mmol, 3.1 equiv) and 3-aminopiperidine-2,6-dionehydrochloride (552 mg, 3.35 mmol, 1.1 equiv) in acetic acid (10.2 mL, 0.3 M) was heated to 90°C overnight. The black reaction mixture was cooled to room temperature and diluted to 20 mLwith water, and subsequently cooled on ice for 30 mm. The resulting slurry was transferred to a50 mL Falcon tube, which was centrifuged at 3500 rpm for 5 mm. The supernatant was discardedand the black solid was transferred to a 250 mL RBF with methanol and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (CH2C12:MeOH (9:1)) to afford the title compound as a white solid (619 mg, 74%). 1H NMR (400 MHz, DMSO-d6) 11.07 (s, 1H), 7.65 (dd,J=8.4, 6.8Hz, 1H), 7.31 (d,J=6.8Hz, 1H), 7.24(d,J=8.4Hz, 1H), 5.06(dd, J= 12.8, 5.4 Hz, 1H), 2.94-2.82 (m, 1H), 2.64-2.43 (m, 2H), 2.08 - 1.97 (m, 1H); MS (ESI)calcd for C13H11N205 [M+H] 275.07, found 275.26. |
| 87% |
With potassium acetate; acetic acid at 90℃; |
General procedure I: IMiD condensation (1190) 2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione (D-1)
General procedure: In a 20 mL glass vial, a mixture of 3-hydroxyphthalic anhydride (500 mg, 3.05 mmol, 1 equiv), potassium acetate (927 mg, 9.44 mmol, 3.1 equiv) and 3-aminopiperidine-2,6-dione hydrochloride (552 mg, 3.35 mmol, 1.1 equiv) in acetic acid (10.2 mL, 0.3 M) was heated to 90 oC overnight. The black reaction mixture was cooled to room temperature and diluted to 20 mL with water, and subsequently cooled on ice for 30 min. The resulting slurry was transferred to a 50 mL Falcon tube, which was centrifuged at 3500 rpm for 5 min. The supernatant was discarded and the black solid was transferred to a 250 mL RBF with methanol and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (CH2Cl2:MeOH (9:1)) to afford the title compound as a white solid (619 mg, 74%).1H NMR (400 MHz, DMSO-d6) δ 11.07 (s, 1H), 7.65 (dd, J = 8.4, 6.8 Hz, 1H), 7.31 (d, J = 6.8 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 5.06 (dd, J = 12.8, 5.4 Hz, 1H), 2.94- 2.82 (m, 1H), 2.64- 2.43 (m, 2H), 2.08- 1.97 (m, 1H); MS (ESI) calcd for C13H11N2O5 [M+H]+ 275.07, found 275.26. |
| 58% |
In 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; |
3 General Procedure 1: Deprotection/Condensation Reaction
General procedure: A suspension of tert-butyl N-(2,6-dioxo-3-piperidyl)carbamate (1 eq.) and the corresponding anhydride (1 eq.) in Trifluoroethanol was heated for 2 h at 150 °C under microwave conditions. After cooling to r.t. the reaction mixture was cooled to -20° C for 4 h. If the desired product did not precipitate after cooling to -20° C, ethyl acetate (3 drops) was added and the mixture kept at -20° C for additional 4 h. The precipitated product was filtered off, washed with ethyl acetate (3 x 2 ml) and dried to constant weight; 2-(2,6-dioxopiperidin-3-yl)hexahydro-1H-isoindole-1,3(2H)-dione, 1; Compound 1 was prepared according to GP1 using 400 mg of tert-butyl N-(2,6-dioxo-3- piperidyl)carbamate to yield 399 mg (86%) of 2-(2,6-dioxopiperidin-3-yl)hexahydro-1H- isoindole-1,3(2H)-dione.1H NMR (500 MHz, DMSO-d6) δ 11.00 (s, 1H), 4.88 (dd, J = 12.8, 5.5 Hz, 1H), 3.05-2.93 (m, 2H), 2.81 (ddd, J = 17.1, 14.0, 5.5 Hz, 1H), 2.52 (ddd, J = 17.0, 4.4, 2.5 Hz, 1H), 2.40 (qd, J = 13.1, 4.4 Hz, 1H), 1.86 (dtd, J = 13.1, 5.4, 2.4 Hz, 1H), 1.78- 1.57 (m, 4H), 1.47-1.19 (m, 4H).13C NMR (126 MHz, DMSO-d6) δ 179.30, 179.21, 173.14, 169.85, 49.22, 31.17, 23.58, 23.39, 21.58, 21.53, 21.48. HRMS: calc. [M-H]- for C13H16N2O4 = 263.1110; found = 263.1165 [M-H]- . |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
